Table 1.
Summary of sildenafil and desmethylsildenafil pharmacokinetic parameters after intravenous administration of a single 10 mg bolus dose to patients with pulmonary arterial hypertension
| Parameter (units)* | Sildenafil(n= 10) | Desmethyl sildenafil(n= 10) |
|---|---|---|
| AUC0–6 (ng h ml−1) | 301.2 (31%) | 123.1 (79%) |
| AUC0–8 (ng h ml−1) | 329.7 (34%) | 147.3 (86%) |
| C0 (ng·ml−1) | 248.4 (48%) | – |
| Cmax (ng ml−1) | 213.3 (45%) | 30.8 (62%) |
| tmax (min) | 5 | 35 |
| t½ (h) | 3.2 ± 1.7 | – |
| CL (l h−1) | 32.2 ± 12.3 | – |
| Vz (l) | 137.3 ± 52.0 | – |
| MR | 0.45 (0.19–2.06) |
Maximum observed plasma drug concentration (Cmax) and time to maximum observed plasma drug concentration (tmax) are unadjusted data. Half-life (t½) was calculated as ln(2)/kel, where kel is the terminal phase rate constant calculated by linear regression of the log-linear concentration–time curve. The area under the curve from time 0 to 6 h (AUC0–6) was calculated using the linear/log trapezoidal method and extrapolated to 8 h (AUC0–8) based on kel. C0 was back-extrapolated using the slope (in semilog scale) of the first two observed concentrations. The AUC0–8 was used to calculate CL (dose/AUC0–8), Vz (dose/AUC0–8×kel) and the metabolite ratio (MR = AUC0–8 desmethylsildenafil/AUC0–8 sildenafil). Results are presented as geometric mean [% coefficient of variance (CV)] for AUC0–6, AUC0–8, C0, and Cmax; median for tmax; arithmetic mean ± SD for t½, CL and Vz, and geometric mean (range) for MR.